The nucleoside compound 1-(2'-deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-5-iodouracil (FIAU) has been described, for example, in U.S. Pat. No. 4,211,773, as an antiviral and an antitumor agent. The disclosure of this patent reference includes methods for the preparation of the compound FIAU and also claims pharmaceutical compositions comprising a general class of pyrimidine analogs, including FIAU, 1-(2'-deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-5-iodocytosine (FIAC) or pharmaceutically acceptable acid addition salts thereof. Cell culture data showing the inhibition of Herpes Simplex Virus (HSV) replication are presented for a variety of nucleoside analogs. In the case of FIAC, in vivo data in mice inoculated with HSV-1 are also presented, showing improved survival rates for those test animals that received FIAC compared with control animals.
Other studies involving the in vitro activity of FIAC and its primary deaminated uracil metabolite, FIAU, against several herpes group viruses, particularly herpes simplex (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV) have been performed. Although not elucidated in definitive detail, FIAC/FIAU (FIAC can be considered the prodrug of FIAU) apparently exert their effect by serving as substrates for viral DNA polymerase. (Cheng, Y.-C. et al. Antimicrobial Agents and Chemotherapy 1981, 20:420-423.) The in vitro ED.sub.90 value for FIAC/FIAU against these viruses ranges from approximately 0.05 .mu.M for HSV-1 to about 0.5 .mu.M for CMV. Typical cellular toxicity concentrations (ID.sub.50) are approximately in the 10 .mu.M range. (Lopez, C. et al. Antimicrobial Agents and Chemotherapy 1980, 17(5):803-806; Schinazi, R. F. et al. Antimicrobial Agents and Chemotherapy 1986, 29:77-84; Colacino, J. M. et al. Antimicrobial Agents and Chemotherapy 1983, 24:505-508; Hantz, O. et al. Antiviral Research 1984, 4:187-189).